title: Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action.
abstract: Impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system is a consistent finding among patients with depression, which can be most sensitively detected with the combined dexamethasone (dex)/corticotrophin releasing hormone (CRH) test. The majority of patients with acute depression shows an exaggerated plasma corticotrophin (ACTH) and cortisol response to this test that normalizes gradually during successful antidepressant therapy. In contrast, persistently high HPA-responses to this challenge are prognostically less favorable. It has been recently questioned, whether this observation applies also to treatment with the atypical antidepressant mirtazapine, as patients treated with this drug showed a distinct attenuation of the endocrine response to the dex/CRH test already after 1 week of treatment. In the present study, we investigated whether the attenuating effect of mirtazapine on the HPA system is an acute pharmacological reaction disappearing after physiological adaptation or whether this effect is related to the antidepressant action of the drug. We examined plasma ACTH and cortisol responses to the dex/CRH test in acutely depressed inpatients treated either with mirtazapine (n=55) or a monoamine reuptake inhibitor (n=105) according to doctor's choice and compared the test results with healthy controls (n=40). Patients treated with monoamine reuptake inhibitors received either selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or the combined serotonin and noradrenalin reuptake inhibitor venlafaxine. We found increased plasma ACTH and cortisol responses to the dex/CRH test in depressed patients compared with healthy controls, but also significantly (p=.017) attenuated plasma cortisol secretion in the mirtazapine group compared to the group of monoamine reuptake inhibitor treated patients. This effect was not significant in male patients. Furthermore this effect was independent of the psychopathological state, but depended on treatment duration. Patient treatment with mirtazapine for up to 7 days resulted in dex/CRH test outcome that was indistinguishable from controls. This effect, however waned as it was not observable in patients treated for a longer period. These results suggest that short-term administration of mirtazapine has immediate but only transient suppressive effects on the HPA system predominantly in women. Our results confirm that dex/CRH tests can be used as predictors of clinical course also under mirtazapine treatment.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany. Electronic address: horstmann@mpipsykl.mpg.de.
authors.forename: Sonja
authors.initials: S
authors.lastname: Horstmann
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Dose
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lucae
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kloiber
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Menke
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hennings
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Derek
authors.initials: D
authors.lastname: Spieler
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010912:Pituitary-Adrenal Function Tests / Q000379:methods; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000324:Adrenocorticotropic Hormone; D000078785:Mirtazapine; D006854:Hydrocortisone